Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Measuring Ostracism-Induced Changes in Consumption of Palatable Food: Feasibility of a Novel Behavioral Task.

Purpose: Ostracism is a highly aversive interpersonal experience. Previous research suggests that it can increase consumption of highly palatable food in some individuals, but decrease it in others. Thus, we developed the Cyberball-Milkshake Task (CMT), to facilitate research investigating individual differences in ostracism's effects on consumption of highly palatable food. We present data on feasibility for the CMT in a sample of young adult women. Materials and Methods: Participants were 22 women, 18-30 years old, reporting very low or very high levels of emotional eating at screening. Participants performed the CMT, which consisted of 12 trials. Each trial included: playing a round of Cyberball (a computerized game of catch with fictitious "other participants" programmed to either include or exclude the participant); viewing a chocolate image; and then consuming a participant-determined amount of milkshake. Participants subsequently played an additional inclusion and exclusion round of Cyberball, each immediately followed by questionnaires assessing current mood and recent Cyberball experience. Results: Cyberball exclusion (vs. inclusion) was associated with large, significant increases in reported ostracism and threats to self-esteem; exclusion's effects on affect were in the expected direction (e.g., increased negative affect), but generally small and non-significant. Milkshake intake was measurable for 95% of participants, on 96% of trials. Intake decreased quadratically across trials, with a steep negative slope for low trial numbers that decreased to the point of being flat for the highest trial numbers. Discussion: The CMT is a generally feasible approach to investigating ostracism's effects on consumption of highly palatable food. The feasibility (and validity) of the CMT may benefit from modification (e.g., fewer trials and longer rounds of Cyberball). Future research should examine whether performance on a modified version of the CMT predicts real-world behavior in a larger sample.

Use of an Individual-Level Approach to Identify Cortical Connectivity Biomarkers in Obsessive-Compulsive Disorder.

BACKGROUND: Existing functional connectivity studies of obsessive-compulsive disorder (OCD) support a model of circuit dysfunction. However, these group-level observations have failed to yield neuroimaging biomarkers sufficient to serve as a test for the OCD diagnosis, predict current or future symptoms, or predict treatment response, perhaps because these studies failed to account for the substantial intersubject variability in structural and functional brain organization. METHODS: We used functional regions, localized in each of 41 individual OCD patients, to identify cortical connectivity biomarkers of both global and dimension-specific symptom severity and to detect functional connections that track changes in symptom severity following intensive residential treatment. RESULTS: Global OCD symptom severity was directly linked to dysconnectivity between large-scale intrinsic brain networks-particularly among the dorsal attention, default, and frontoparietal networks. Changes within a subset of connections among these networks were associated with symptom resolution. Additionally, distinct and nonoverlapping cortical connectivity biomarkers were identified that were significantly associated with the severity of contamination/washing and responsibility for harm/checking symptoms, highlighting the contribution of dissociable neural networks to specific OCD symptom dimensions. By contrast, when we defined functional regions conventionally, using a population-level brain atlas, we could no longer identify connectivity biomarkers of severity or improvement for any of the symptom dimensions. CONCLUSIONS: Our findings would seem to encourage the use of individual-level approaches to connectivity analyses to better delineate the cortical and subcortical networks underlying symptom severity and improvement at the dimensional level in OCD patients.

Acute change in anterior cingulate cortex GABA, but not glutamine/glutamate, mediates antidepressant response to citalopram.

Little is known about the acute effects of antidepressant treatments on brain glutamate and gamma-amino-butyric acid (GABA) levels, and their association with clinical response. Using proton magnetic resonance spectroscopy (1H-MRS) we examined longitudinally the effects of citalopram on glutamine/glutamate ratios and GABA levels in the pregenual anterior cingulate cortex (pgACC) of individuals with major depressive disorder (MDD). We acquired 1H-MRS scans at baseline and at days 3, 7, and 42 of citalopram treatment in nineteen unmedicated individuals with MDD. Ten age- and sex-matched non-depressed comparison individuals were scanned once. The association between 1) baseline metabolites and 2) change in metabolites from baseline to each time point and clinical response (change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 42) was assessed by longitudinal regression analysis using generalized estimating equations. Contrary to our hypotheses, no significant associations emerged between glutamate metabolites and clinical response; however, greater increases (or smaller decreases) in pgACC GABA levels from baseline to days 3 and 7 of citalopram treatment were significantly associated with clinical response. These findings suggest that an acute change in GABA levels in pgACC predicts, and possibly mediates, later clinical response to citalopram treatment in individuals with MDD.